Ellegood Jacob, Nakai Nobuhiro, Nakatani Jin, Henkelman Mark, Takumi Toru, Lerch Jason
Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario Canada (J.E., R.M.H., J.L.).
RIKEN Brain Science Institute, Wako, Saiama, Japan (N.N., T.T.).
Autism Res. 2015 Oct;8(5):545-55. doi: 10.1002/aur.1469. Epub 2015 Mar 7.
Paternally and maternally inherited deletions and duplications of human chromosome 15q11-13 are relatively common in the human population. Furthermore, duplications in the 15q region are often associated with autism. Both maternal and paternal interstitial 15q11-13 duplication mouse models have been previously created, where several behavioral differences were found in the paternal duplication (patDp/+) mouse but not in the maternal duplication (matDp/+). These included decreased sociability, behavioral inflexibility, abnormal ultrasonic vocalizations, decreased spontaneous activity, and increased anxiety. Similarly, in the current study, we found several anatomical differences in the patDp/+ mice that were not seen in the matDp/+ mice. Regional differences that are evident only in the paternal duplication are a smaller dentate gyrus and smaller medial striatum. These differences may be responsible for the behavioral inflexibility. Furthermore, a smaller dorsal raphe nucleus could be responsible for the reported serotonin defects. This study highlights consistency that can be found between behavioral and anatomical phenotyping.
人类15号染色体q11 - 13区域父源和母源遗传的缺失与重复在人群中相对常见。此外，15q区域的重复常与自闭症相关。此前已构建了母源和父源15q11 - 13间质性重复小鼠模型，在父源重复（patDp/+）小鼠中发现了一些行为差异，而母源重复（matDp/+）小鼠中未发现。这些差异包括社交性降低、行为灵活性下降、异常超声发声、自发活动减少以及焦虑增加。同样，在本研究中，我们在patDp/+小鼠中发现了一些matDp/+小鼠中未出现的解剖学差异。仅在父源重复中明显的区域差异是齿状回较小和内侧纹状体较小。这些差异可能是行为灵活性下降的原因。此外，较小的中缝背核可能是所报道的血清素缺陷的原因。这项研究突出了行为表型和解剖学表型之间的一致性。
